Analysis: there are grounds for optimism in research findings on how patients have responded to the use of Lecanemab and HRT treatments
We all have fears in life, and the nature of those fears can change with life stage and circumstance. Among people in later-middle and older ages in the US, the loss of independence and inability to manage one's own daily life, both very clearly linked to dementia, are among the greatest worries reported. In the UK, dementia is the most feared condition.
Alzheimer's disease is the most common form of dementia, and is made-up of a spectrum of deficits. These can be in memory, certain language and physical skills, recognition, attention, categorisation and others, and must be sufficient to cause problems in everyday life. The stereotype of forgetfulness doesn't quite capture it and Alzheimer's disease can be diagnosed without amnesia of any type. It can also include changes to mood, personality, and other psychological characteristics. For a diagnosis of Alzheimer's disease, the changes must be ongoing and progressive.
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From RTÉ Radio 1's Morning Ireland. Dr Laura O'Philbin from the Alzheimer Society of Ireland on a new drug that could possibly slow the destruction of the brain by the disease
The disease becomes increasingly prevalent with age. 3% of 65 to 74 year-olds have Alzheimer's disease and this rises to 17% of 75 to 84 year-olds, and 32% of those aged 85 plus. As life expectancy increases, the number of people living with Alzheimer's disease is expected to increase. The extension of life expectancy is a wonderful testament to advances in medical science and improvements in lifestyle, but adding years to life is of limited value unless we are also adding life to those years.
When we discuss the risk of Alzheimer's disease, the message has typically been the same for years: there are steps we can take to reduce our risk, such as taking care of body and mind, but the disease is a gradual process of decline once it develops. Over the last decades there have been several reports of promising therapies, and several false dawns. The last time a medication was licensed for use in Alzheimer's disease was galantamine (or Razadyne) in 2004.
But recent developments may change this. While the picture is not straightforward or clearcut, and there are caveats and uncertainties, there are grounds for optimism. Last month, the US Food and Drugs Administration approved the use of Lecanemab. This decision was based on a paper published recently which reports on the results of a trial of Lecanemab, which counters a protein called β-amyloid.
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From RTÉ News, new Alzheimer's drug shown to slow cognitive decline
Organically, Alzheimer's disease is associated with the presence in the brain of β-amyloid. The exact link between β-amyloid and Alzheimer's disease symptoms is unclear, but it is likely that's β-amyloid interferes with communication between brain cells, contributing to cell degeneration and death.
This was a large study, including people with diagnosis of early Alzheimer's disease and evidence of β-amyloid accumulations. Half were given intravenous Lecanemab fortnightly, the other half being given placebo. Before treatment, and 18 months later, participants completed measures of cognitive function and β-amyloid levels. The study results showed that the Lecanemab group did better than the placebo group on the main measures of cognitive function, and on levels of β-amyloid. Given this, the drug seems to work.
But it needs to be stressed that this is not a silver bullet. Lecanemab appears to have a real but quite moderate effect as it slowed cognitive decline by about 27% compared to the placebo group. It's not a cure, and it doesn't halt decline and the condition remains inexorably progressive with this drug.
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From RTÉ Radio 1's News At One, new Alzheimer's drug hailed as 'beginning of the end' in search for treatment
On the other hand, this level of slowing would extend both lives and good quality life years appreciably. That this form of drug has an effect also opens the way for further research. This will surely not be the last such substance to be developed and trialled so we can hope for better, more effective ones all the time.
There are, of course, issues with its widespread use. There were a number of cases of serious side effects, including heart and brain problems. These must be a concern, and would require monitoring. It's also clear public health systems are not staffed or equipped enough to deliver fortnightly infusions and monitor side effects for large numbers of people. In addition, Lecanemab is expensive and will cost between €11,288 and and €33,865,000 per year per patient. Considering the relatively modest effects at this time, and the already existing pressures on health budgets, it seems unlikely this treatment will be prioritized.
It's probably unrealistic to expect this drug to benefit many Alzheimer's disease sufferers in the short term. But for the first time in quite a while, there seems real grounds for cautious optimism about an intervention that can appreciably slow the process once it has begun
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From RTÉ Radio 1's Liveline, interview with Prof. Anne-Marie Minihane who has been studying if HRT can reduce the risk of Alzheimer's in women
Another study provides further grounds for optimism. It examines the association between Alzheimer's disease-related features (cognitive test performance and brain volume) and hormone replacement therapy (HRT) specifically in women who carry a form of gene called APOEε4. As noted above, age is a marked risk factor for Alzheimer's disease, but is not the only one. The prevalence of the disease is higher in women (though this may be because women live longer) and it is also higher in those with the APOEε4 gene type.
The study analysed data from 1,906 people across Europe, and found that women carrying APOEε4, who were prescribed HRT in the menopausal transition, went on to show less decline in brain volume and in cognitive functioning tests than did others in the study. This is not conclusive – the study is looking back over data previously gathered, and does not assess Alzheimer's disease directly - but it is very promising, and has prompted follow-up experimental research to further investigate this potential link.
These two developments – in their own ways – offer hope for new fronts to be opened and new weapons deployed against a condition which is a remorseless destroyer. There is greater hope today than there was a year ago, and that is worthy of celebration in itself.
The views expressed here are those of the author and do not represent or reflect the views of RTÉ
